The compounds of the present invention 4-((1R,3S)-6-Chloro-3-phenyl-indan-1-yl)-1,2,2-trimethyl-piperazine (I) and 1-((1R,3S)-6-Chloro-3-phenyl-indan-1-yl)-3,3-dimethyl-piperazine (II) hereinafter referred to as Compound (I) and (II) have the respective molecular structures depicted below.

A group of trans isomers of 3-aryl-1-(1-piperazinyl)indanes substituted in the 2- and/or 3-position of the piperazine ring has been described in WO 93/22293 and in Klaus P. Bøgesø, Drug Hunting, the Medicinal Chemistry of 1-piperazino-3-phenylindans and Related Compounds, 1998, ISBN 87-88085-10-4 (cf. e.g. compound 69 in table 3, p. 47 and in table 9A, p. 101). The compounds are described as having high affinity for dopamine D1 and D2 receptors and the 5-HT2 receptor and are suggested to be useful for treatment of several diseases in the central nervous system, including schizophrenia.
Trans racemic 4-((6-Chloro-3-phenyl-indan-1-yl)-1,2,2-trimethyl-piperazine and trans racemic 1-(6-Chloro-3-phenyl-indan-1-yl)-3,3-dimethyl-piperazine may e.g. be synthesized analogously to the methods outlined in Bøgesø et al., J. Med. Chem., 1995, 38, p. 4380-4392 and in WO 93/22293. Manufacture of Compound (I) by resolvation of trans racemic 4-((6-Chloro-3-phenyl-indan-1-yl)-1,2,2-trimethyl-piperazine has been described by Bøgesø et al. in J. Med. Chem., 1995, 38, p. 4380-4392, see table 5, compound (−)-38. The process described comprises the use of (+)-ditoluoyl tartaric acid for resolvation in ethylacetate, and Compound (I) is isolated as the fumarate salt.
The synthesis of Compound (II) from optically pure starting materials has been described in WO 2005/016900, WO 2005/016901 and WO 2006/086984. Synthesis of Compound (I) from Compound (II) by N-alkylation is disclosed in WO 2005/016900 (p. 31, example 12). A crystalline hydrogen tartrate salt of Compound (II) has been disclosed in WO 2006/086985.
Bøgesø et al., J. Med. Chem., 1995, 38, p. 4380-4392 discloses that Compound (I) is a potent D1/D2 antagonists showing some D1 selectivity in vitro while in vivo it is equipotent as D1 and D2 antagonist. The compound is also described as a potent 5-HT2 antagonist and as having high affinity for α1 adrenoceptors. As disclosed in WO 2005/016901 Compound (II) displays a similar receptor profile and pharmacological activity as Compound (I).